The short version of sublimation fits in a sentence. The long version — which is the one that helps — is below.
Reviewed 2026-08-01. Anything still debated is marked as such rather than presented as settled.
A formulation often contains excipients that protect the active ingredient during freezing and drying. Bulking agents provide structure, while lyoprotectants stabilize sensitive molecules. The freezing step can produce ice crystals whose size and distribution affect the drying rate, and cycle design includes freezing, annealing, and drying phases. If the product temperature rises above a critical value, the cake may collapse or lose its porous structure. Successful lyophilization therefore depends on the interaction between formulation, equipment, and cycle design.
Lyophilization is a dehydration process that removes water from a frozen material by sublimation under low pressure. The material is first frozen to convert liquid water into ice. Next, the pressure is reduced below the triple point of water so that ice changes directly into vapor without passing through a liquid phase. This step is called primary drying. The result is a porous solid or cake that retains the original shape of the frozen solution.
Secondary drying removes bound water that remains after ice sublimation. Shelf temperature is raised gradually while pressure remains low, reducing water content to a target range. Over-drying can cause brittleness or electrostatic issues, while under-drying affects stability. The endpoint is often judged by pressure rise tests, temperature measurements, or water content analysis. Scale-up depends on matching heat and mass transfer across equipment sizes. Small changes in shelf temperature or pressure can alter cycle length substantially.
Lyophilization, or freeze-drying, removes water from a material by freezing it and then lowering pressure so ice changes directly to vapor. The process relies on sublimation, the phase transition from solid to gas without an intervening liquid state. It is used for heat-sensitive materials that would degrade in conventional drying. The three stages are freezing, primary drying, and secondary drying, each with distinct temperature and pressure requirements. In practice, cycle design balances these variables.
| Property | Value | Notes |
|---|---|---|
| Common synonyms | Freeze-drying, lyophilisation | Lyophilization is the American spelling; lyophilisation is British |
| Primary drying mechanism | Sublimation of ice | Occurs under vacuum below the triple point |
| Typical chamber pressure | 0.05-0.5 mbar | Range depends on product and equipment |
| Typical shelf temperature during freezing | -40 to -20 °C | Lower temperatures may be used for labile products |
| Resulting product form | Porous cake or powder | Appearance depends on formulation and cycle |
The process generally proceeds in three stages: freezing, primary drying, and secondary drying. During freezing, controlled cooling converts water into ice and may also crystallize or vitrify solutes. In primary drying, the pressure is lowered below the triple point, and heat is supplied so ice sublimes directly to vapor. Secondary drying removes water that remains bound to the solid matrix, yielding a low final water content. Product temperature must stay below the collapse or glass transition temperature to maintain structure. Cycle design therefore balances shelf temperature, chamber pressure, and time.
Freeze-drying is used for materials whose activity or structure depends on low temperature and low water content. Examples include certain biologics, diagnostic reagents, starter cultures, coffee, and porous inorganic precursors. The dried product forms a cake whose porosity aids rapid wetting and dissolution. Main drawbacks are high energy use, long cycle times, and sensitivity to formulation and equipment variation. Questions remain about how freezing rates and ice morphology affect batch uniformity, especially when moving from laboratory to production scale.
Lyophilization, also called freeze-drying, is a dehydration process in which a solvent, usually water, is frozen and then removed by sublimation under reduced pressure. The method preserves heat-sensitive materials that would degrade in conventional drying. Large-scale use grew during the mid-twentieth century for blood plasma and antibiotics, and it later expanded to vaccines, enzymes, foods, and advanced materials. The process produces a dry, porous solid that usually reconstitutes rapidly. It is distinct from simple evaporation because the solvent bypasses the liquid phase during primary removal.
Lyophilization, also called freeze-drying, removes water from a frozen material by sublimation under reduced pressure. The process begins with freezing, which converts free water into ice and may also produce a glassy phase. Primary drying then lowers chamber pressure so ice sublimes directly to vapor without passing through a liquid stage. Secondary drying raises the temperature modestly to remove bound water. The result is a porous, dry solid that usually reconstitutes quickly. Each stage influences pore structure, residual moisture, and stability.
The physics of lyophilization depends on phase boundaries and heat and mass transfer. During primary drying, heat supplied to the product must equal the latent heat of sublimation, while water vapor moves through the drying cake to the condenser. If shelf temperature or pressure is set too high, the ice front can exceed the collapse temperature, causing meltback or pore collapse. If conditions are too cold, drying slows and costs rise. Formulation excipients, vial geometry, and freezing rate alter these limits.
Lyophilization is a dehydration process that removes water from a frozen material by sublimation under low pressure. The material is first frozen so that water becomes ice; then the surrounding pressure is lowered below the vapor pressure of ice. Heat is applied gently so ice changes directly to vapor without passing through a bulk liquid phase. The vapor is collected on a cold condenser, leaving a dry porous matrix. This process differs from simple evaporation because the material remains frozen during the main drying stage.
The process usually has three stages: freezing, primary drying, and secondary drying. Freezing sets the ice crystal structure and can determine pore size in the final cake. Primary drying removes free ice by sublimation at low pressure and low shelf temperature. Secondary drying removes bound water by raising the shelf temperature, although some water may remain as part of the solid. Cycle parameters depend on formulation, fill volume, vial type, and equipment performance.
The physical chemistry of freezing influences whether a formulation forms an amorphous glass or a crystalline solid. Amorphous systems can collapse if product temperature rises above the glass transition temperature of the freeze concentrate. Crystalline systems may show eutectic melting, where ice and solute melt together at a fixed temperature. Formulators add bulking agents, lyoprotectants, and buffers to preserve structure and biological activity. The optimum cycle keeps product temperature below critical thresholds during primary drying while allowing efficient sublimation.
Lyophilization, also known as freeze-drying, is a process that removes water from a material by freezing it and then reducing pressure to allow ice to sublimate directly into vapor. The method begins with a freezing step that solidifies the water content. Next, primary drying lowers the pressure below the triple point of water, enabling sublimation without passing through a liquid phase. A final secondary drying step removes bound water through desorption. This sequence produces a dry, porous cake that can be reconstituted later.
The process relies on the phase diagram of water, where the triple point marks the conditions at which ice, liquid water, and vapor coexist. By maintaining pressure below this point, typically around 0.01 to 0.1 millibar, sublimation becomes the dominant mechanism. Formulations often include excipients such as sugars or polymers that act as lyoprotectants and bulking agents. These additives help preserve the structure of the active ingredient and prevent collapse during drying. The choice of excipient and freezing rate influences the final cake morphology and stability.
During 1986, Syed Zaki Salahuddin, Dharam Ablashi, and Robert Gallo cultivated peripheral blood mononuclear cells from patients with AIDS and lymphoproliferative illnesses. Short-lived, large, refractile cells that frequently contained intranuclear and/or intracytoplasmic inclusion bodies were documented. Electron microscopy revealed a novel virus that they named human B-lymphotropic virus (HBLV). Shortly after its discovery, Ablashi et al. described five cell lines that can be infected by the newly discovered HBLV. They published that HSB-2, a particular T-cell line, is highly susceptible to infection. Ablashi's pioneering research concluded by suggesting that the virus name be changed from HBLV to HHV-6, in accord with the published provisional classification of herpes viruses. Years later, HHV-6 was divided into subtypes. Early research (1992) described two very similar, yet unique variants: HHV-6A and HHV-6B. The distinction was warranted due to unique restriction endonuclease cleavages, monoclonal antibody reactions, and growth patterns. HHV-6A includes several adult-derived strains and its disease spectrum is not well defined, although it is thought by some to be more neurovirulent. HHV-6B is commonly detected in children with roseola infantum, as it is the etiologic agent for this condition. Within these two viruses is a sequence homology of 95%. In 2012, HHV-6A and HHV-6B were officially recognized as distinct species.
== Triglyceride synthesis == Triglycerides are synthesized by esterification of fatty acids to glycerol. Fatty acid esterification takes place in the endoplasmic reticulum of cells by metabolic pathways in which acyl groups in fatty acyl-CoAs are transferred to the hydroxyl groups of glycerol-3-phosphate and diacylglycerol. Three fatty acid chains are bonded to each glycerol molecule. Each of the three -OH groups of the glycerol reacts with the carboxyl end of a fatty acid chain (-COOH). Water is eliminated and the remaining carbon atoms are linked by an -O- bond through dehydration synthesis. Both the adipose tissue and the liver can synthesize triglycerides. Those produced by the liver are secreted from it in the form of very-low-density lipoproteins (VLDL). VLDL particles are secreted directly into blood, where they function to deliver the endogenously derived lipids to peripheral tissues. Enzymatically, the glycerol-3-phosphate pathway occurs in the endoplasmic reticulum where it is acylated by glycerol-3-phosphate acyltransferase (GPAT), 1-acylglycerol-3-phosphate acyltransferase (AGPAT), subsequently dephosphorylated by lipin, and finally converted by diacylglycerol acyltransferase (DGAT).
1993/3114) Education (Annual Consideration of Ballot on Grant-Maintained Status) (England) Order 1993 (S.I. 1993/3115) Registration of Births, Deaths and Marriages (Fees) Order 1993 (S.I. 1993/3116) Vocational Training (Tax Relief) (Amendment No. 2) Regulations 1993 (S.I. 1993/3118) Foot–and–Mouth Disease (Amendment) (No. 2) Order 1993 (S.I. 1993/3119) Civil Courts (Amendment No. 2) Order 1993 (S.I. 1993/3120) Income Support (General) Amendment (No. 4) Regulations 1993 (S.I. 1993/3121) Appointment of Judges as Arbiters (Fees) (Scotland) Order 1993 (S.I. 1993/3125) Insurance Companies (Switzerland) Regulations 1993 (S.I. 1993/3127) Act of Sederunt (Summary Suspension) 1993 (S.I. 1993/3128) Durham and Tyne and Wear (County and District Boundaries) (Variation) Order 1993 (S.I. 1993/3129) National Savings Bank (Amendment) Regulations 1993 (S.I. 1993/3130) National Savings Stock Register (Amendment) (No. 2) Regulations 1993 (S.I. 1993/3131) Savings Certificates (Yearly Plan) (Amendment) Regulations 1993 (S.I. 1993/3132) Savings Certificates (Amendment) Regulations 1993 (S.I. 1993/3133) Severn Bridges Tolls Order 1993 (S.I. 1993/3135) Environmentally Sensitive Areas (Argyll Islands) Designation Order 1993 (S.I. 1993/3136) Merchant Shipping (Registration, etc.) Act 1993 (Commencement No. 1 and Transitional Provisions) Order 1993 (S.I. 1993/3137) Merchant Shipping (Registration of Ships) Regulations 1993 (S.I. 1993/3138) Combined Probation Areas (Suffolk) Order 1993 (S.I. 1993/3139) Mid Essex Community Health National Health Service Trust Dissolution Order 1993 (S.I.
Recently, copper alloys have become important netting materials in aquaculture because they are antimicrobial (i.e., they destroy bacteria, viruses, fungi, algae, and other microbes) and they therefore prevent biofouling (i.e., the undesirable accumulation, adhesion, and growth of microorganisms, plants, algae, tubeworms, barnacles, mollusks, and other organisms). By inhibiting microbial growth, copper alloy aquaculture cages avoid costly net changes that are necessary with other materials. The resistance of organism growth on copper alloy nets also provides a cleaner and healthier environment for farmed fish to grow and thrive.
The abdication of Kings Charles IV of Spain and Ferdinand VII of Spain and the installation of Napoleon's brother as King José provoked civil wars and revolutions, leading to the independence of most of Spain's mainland American colonies. In Spanish America, many local elites formed juntas and set up mechanisms to rule in the name of Ferdinand VII, whom they considered the legitimate Spanish monarch. The outbreak of the Spanish American wars of independence in most of the empire was a result of Napoleon's destabilizing actions in Spain, and led to the rise of strongmen in the wake of these wars. The defeat of Napoleon at Waterloo in 1815 caused an exodus of French soldiers into Latin America, where they joined ranks with the armies of the independence movements. While these officials had a role in various victories such as the Capture of Valdivia (1820), some are held responsible for significant defeats at the hands of the royalists, as was the case at the Second Battle of Cancha Rayada (1818). In contrast, the Portuguese royal family escaped to Brazil and established the court there, resulting in political stability for Portuguese America. In 1816, Brazil was proclaimed an equal part of the United Kingdom of Portugal, Brazil and the Algarves, paving the way to Brazilian independence six years later.
Sources: en.wikipedia.org
=== Cobaltocene and derivatives === Cobaltocene, Co(C5H5)2, is a metallocene, the cobalt analogue of ferrocene. It is a dark purple solid. Cobaltocene has 19 valence electrons, one more than usually found in organotransition metal complexes, such as its very stable relative, ferrocene, in accordance with the 18-electron rule. This additional electron occupies an orbital that is antibonding with respect to the Co–C bonds. Consequently, many chemical reactions of Co(C5H5)2 are characterized by its tendency to lose this "extra" electron, yielding a very stable 18-electron cation known as cobaltocenium. Many cobaltocenium salts coprecipitate with caesium salts, and cobaltocenium hydroxide is a strong base that absorbs atmospheric carbon dioxide to form cobaltocenium carbonate. Like the alkali metals, cobaltocene is a strong reducing agent, and decamethylcobaltocene is stronger still due to the combined inductive effect of the ten methyl groups. Cobalt may be substituted by its heavier congener rhodium to give rhodocene, an even stronger reducing agent. Iridocene (involving iridium) would presumably be still more potent, but is not very well-studied due to its instability.
Dissociation of the target mRNA strand from RISC after the cleavage allows more mRNA to be silenced; this dissociation process is likely to be promoted by extrinsic factors driven by ATP hydrolysis. Sometimes, cleavage of the target mRNA molecule does not occur. In some cases, the endonucleolytic cleavage of the phosphodiester backbone may be suppressed by mismatches of siRNA and target mRNA near the cleaving site. Other times, the Argonaute proteins of the RISC lack endonuclease activity even when the target mRNA and siRNA are perfectly paired. In such cases, gene expression will be silenced by an miRNA-induced mechanism instead.
Mahathir was the CEO and chairman, and hence a senior adviser, for many flagship Malaysian companies such as Proton, Perdana Leadership Foundation and Malaysia's government-owned oil and gas company Petronas. He did not receive any remuneration for his advisory positions. He was also made Universiti Teknologi Petronas (UTP) Chancellor in 2004, succeeding Raja Mohar Raja Badiozaman. On 15 June of the same year, Mahathir was appointed chairman of the NAM Business Council International Advisory Panel. In 2006, Mahathir co-founded The Loaf bakery with Motoko Resources Sdn Bhd, opening its first store in Telaga Harbour, Langkawi, before expanding to 12 outlets in locations such as KLCC, Pavilion, Sogo, and Empire Shopping Gallery. He also served as The Loaf's chairman. Despite his business ventures, Mahathir remained an influential figure, and his views on national matters continued to draw attention. Mahathir and Abdullah had a major fallout over Proton in 2005. While Abdullah was attempting to reform the company and implemented high import tariffs on foreign cars, Mahathir accused Abdullah's government of cronyism in relation to import licences. Proton's chief executive, a Mahathir ally, had been sacked by the company's board. With Abdullah's blessing, Proton then sold one of its prise assets, the motorcycle company MV Agusta, which was bought on Mahathir's advice.
Codtrace. Archived 1 February 2016 at the Wayback Machine. fishbase.org – Scientific Names for Gadus Fisheries Heritage website, Newfoundland and Labrador (archived) Long term trends in Norwegian cod fisheries – the pioneers Species factsheet on cod from the UK Sea Fish Industry Authority (PDF, 2MB) "Cod" . New International Encyclopedia. 1905.
Sources: en.wikipedia.org
A laboratory study on rats produced by the Armed Forces Radiobiology Research Institute showed that, after a study period of 6 months, rats treated with depleted uranium coming from implanted pellets, comparable to the average levels in the urine of Desert Storm veterans with retained DU fragments, had developed a significant tendency to lose weight with respect to the control group. Substantial amounts of uranium were accumulating in their brains and central nervous systems, and showed a significant reduction of neuronal activity in the hippocampus in response to external stimuli. The conclusions of the study show that brain damage from chronic uranium intoxication is possible at lower doses than previously thought. Results from computer-based neurocognitive tests performed in 1997 showed an association between uranium in the urine and "problematic performance on automated tests assessing performance efficiency and accuracy." A 2021 report concluded that uranium from exploding munitions did not lead to Gulf War illness (GWI) in veterans deployed in the 1991 Persian Gulf War. The study found no differences in secretion of uranium isotopic ratios from those meeting the standard-case definitions of GWI and control veterans without GWI. The researchers say that the most likely remaining causes for GWI are widespread low-level exposure to sarin nerve gas released by the destruction of Iraqi chemical weapons storage facilities in January 1991.
=== Energy expenditure === Adrenergic agonists that work on the beta-2 adrenergic receptor increase energy expenditure. Although some such as clenbuterol are used without medical approval for weight loss, none have achieved approval for this indication due to cardiac risks. The anti-obesity effects of amphetamines, besides acting on the brain to reduce energy intake, are also mediated by the beta-2 adrenergic receptor. Ephedrine (and related compounds that are also active ingredients in ephedra preparations) exert their effects by acting directly and indirectly as adrenergic agonists. The discontinued drug 2,4-dinitrophenol works by increasing energy expenditure by decreasing the efficiency of mitochondria (uncoupling agent). A prodrug of DNP, HU6, has been tested in clinical trials for weight loss and fatty liver disease. Fibroblast growth factor-21 receptor agonists and drugs increasing FGF-21 activity are being investigated for obesity-related diseases; they can increase energy expenditure and several have been tested in humans. Thyroid hormones, another early weight loss drug, also raised energy expenditure but ceased to be used for weight loss due to cardiac risks and other adverse effects. Selective thyromimetics that work on the thyroid hormone receptor beta may be able to exert some of the beneficial thermogenic effects of thyroid hormones with fewer adverse effects, but none have received approval as of 2023.
=== Reports by the Western media === On 9 August 2008, the Associated Press reported that one Russian conscript said he was suddenly deployed to South Ossetia instead of expected exercises in North Ossetia. On 18 August 2008, Le Figaro published the report by journalist who was told by a young Russian soldier at some checkpoint in Georgia that he came from Shali, Chechen Republic and that they left on 5 August 2008. On 27 August 2008, the Financial Times quoted an unnamed Russian colonel as saying: "We were called to react to alarm on the night of 7th. [...] There was such an escalation of events that I cannot remember exactly when we entered the tunnel." On 29 August 2008, journalist Robert Parsons wrote in The Guardian that Russian servicemen deployed in Georgia had told him that they had been preparing for the war for weeks. In September 2008, The New York Times quoted anonymous American official as having stated that the western intelligence had information that two battalions of the 135th Regiment could have entered South Ossetia on the night of August 7. In May 2009, the United States Department of State official Matthew Bryza told Echo of Moscow that the United States knew that the Russian tank deployments to South Ossetia began in 2005 and these weaponry were used in August 2008 invasion. He confirmed that Russian tanks were entering South Ossetia before 7 August 2008, but he could not say the exact number of incoming Russian tanks on 7 August.
Sources: en.wikipedia.org
Lyophilization removes water by sublimation from a frozen material, while evaporation changes liquid water into vapor. The low-pressure freezing step avoids the liquid phase and can preserve heat-sensitive structures.
Vacuum lowers the pressure below the triple point of water, allowing ice to sublimate directly into vapor. It also helps remove water vapor from the product chamber and shortens primary drying.
Many aqueous solutions and suspensions can be freeze-dried, but some formulations collapse or do not form a stable cake. The process requires careful formulation and cycle development.
Conventional drying uses heat to evaporate liquid water, often at temperatures that can degrade sensitive materials. Lyophilization freezes the material first and then removes water by sublimation under vacuum. This avoids prolonged exposure to liquid water and high heat.